This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. neurodegenerative disease that is caused by a CAG expansion within the huntingtin gene. It affects about 30000 people in the USA. Despite significant advances in our understanding of HD since identification of the gene in 1993, neuroprotective therapies are not available. Aberrant iron metabolism is implicated in the pathogenesis of neurodegenerative diseases including HD and Parkinson's disease. Theories have centered on excess iron promoting oxidative stress and cell negeneration. However, a clear understanding of the cell and subcellular locations of these processes as well as why brain iron is increased in HD is lacking. Our preliminary data suggests that alterations in iron metabolism occur early in HD and that specific modulation of iron metabolism is neuroprotective.